Glucagon-like peptide-1 (7-36) amide as a novel neuropeptide

Although earlier studies indicated that GLP-1 (7-36) amide was an intestina l peptide with a potent effect on glucose-dependent insulin secretion, late r on it was found that several biological effects of this peptide occur in the brain, rather than in peripheral tissues. Thus, proglucagon is expresse d in pancreas, intestine, and brain, but post translational processing of t he precursor yields different products in these organs, glucagon-like pepti de-1 (7-36) amide being one of the forms produced in the brain. Also, GLP-1 receptor cDNA from human and rat brains has been cloned and sequenced, and the deduced amino acid sequences are the same as those found in pancreatic islets. Through these receptors, GLP-1 (7-36) amide from gut or brain sour ces induces its effects on the release of neurotransmitters from selective brain nuclei, the inhibition of gastric secretion and motility, the regulat ion of food and drink intake, thermoregulation, and arterial blood pressure . Central administration (icv) of GLP-1 (7-36) amide produces a marked redu ction in food and water intake, and the colocalization of the GLP-1 recepto r, GLUT-2, and glucokinase mRNAs in hypothalamic neurons involved in glucos e sensing suggests that these cells may be involved in the transduction of signals needed to produce a state of fullness. In addition, GLP-1 (7-36) am ide inhibits gastric acid secretion and gastric emptying, but these effects are not found in vagotomized subjects, suggesting a centrally mediated eff ect. Similar results have been found with the action of this peptide on art erial blood pressure and heart rate in rats. Synthesis of GLP-1 (7-36) amid e and its own receptors in the brain together with its above mentioned cent ral physiological effects imply that this peptide may be considered a neuro peptide. Also, the presence of GLP-1 (7-36) amide in the synaptosome fracti on and its calcium-dependent release by potassium stimulation, suggest that the peptide may act as a neurotransmitter although further electrophysiolo gical and ultrastructural studies are needed to confirm this possibility.